LP1 from Lentinula edodes C(91-3) Induces Autophagy, Apoptosis and Reduces Metastasis in Human Gastric Cancer Cell Line SGC-7901.

LP1 from Lentinula edodes C(91-3) Induces Autophagy, Apoptosis and Reduces Metastasis in Human Gastric Cancer Cell Line SGC-7901.
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香菇 C91-3 的 LP1 诱导人胃癌细胞系 SGC-7901 中的自噬、细胞凋亡并减少转移

DOI:
10.3390/ijms19102986
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发表时间:
2018-09-30
影响因子:
5.6
通讯作者:
Huang M
Huang M
中科院分区:
生物学2区
文献类型:
--
作者:
Batool S;Joseph TP;Hussain M;Vuai MS;Khinsar KH;Din SRU;Padhiar AA;Zhong M;Ning A;Zhang W;Cao J;Huang M

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本研究旨在阐明香菇菌株C91-3的Latcripin 1(LP 1)对胃癌细胞株SGC-7901和BGC-823的抗肿瘤作用及其可能的分子机制。采用细胞计数试剂盒-8(CCK-8)测定细胞活力;相差显微镜观察细胞形态变化;透射电子显微镜和荧光显微镜观察细胞自噬情况。流式细胞仪检测细胞凋亡和细胞周期;创伤愈合实验、transwell迁移实验和侵袭实验检测LP 1对胃癌细胞迁移和侵袭的影响。在本文中,我们发现LP 1通过形成自噬体和轻链3(LC 3 I)转化为LC 3 II来诱导自噬。LPS 1可上调自噬相关基因(Atg 7、Atg 5、Atg 12、Atg 14)和Beclin 1的表达,上调和下调促凋亡蛋白(Bax)和抗凋亡蛋白(Bcl-2)的表达,沿着Caspase-3的激活。在较低剂量下,LP 1已显示将细胞阻滞在细胞周期的S期,并降低基质金属蛋白酶MMP-2和MMP-9的表达水平。此外,它还被证明可以调节最受阻碍的胃癌途径之一,即蛋白激酶B/哺乳动物雷帕霉素靶蛋白(Akt/mTOR)通道的磷酸化并导致细胞死亡。这些结果表明,LP 1作为一种潜在的天然抗癌剂,用于探索胃癌的治疗,并作为进一步的体外和体内研究的竞争者。
Present study aimed to elucidate the anticancer effect and the possible molecular mechanism underlying the action of Latcripin 1 (LP1), from the mushroom Lentinula edodes strain C91-3 against gastric cancer cell lines SGC-7901 and BGC-823. Cell viability was measured by Cell Counting Kit-8 (CCK-8); morphological changes were observed by phase contrast microscope; autophagy was determined by transmission electron microscope and fluorescence microscope. Apoptosis and cell cycle were assessed by flow cytometer; wound-healing, transwell migration and invasion assays were performed to investigate the effect of LP1 on gastric cancer cell’s migration and invasion. Herein, we found that LP1 resulted in the induction of autophagy by the formation of autophagosomes and conversion of light chain 3 (LC3I into LC3II. LP1 up-regulated the expression level of autophagy-related gene (Atg7, Atg5, Atg12, Atg14) and Beclin1; increased and decreased the expression level of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2) proteins respectively, along with the activation of Caspase-3. At lower-doses, LP1 have shown to arrest cells in the S phase of the cell cycle and decreased the expression level of matrix metalloproteinase MMP-2 and MMP-9. In addition, it has also been shown to regulate the phosphorylation of one of the most hampered gastric cancer pathway, that is, protein kinase B/mammalian target of rapamycin (Akt/mTOR) channel and resulted in cell death. These findings suggested LP1 as a potential natural anti-cancer agent, for exploring the gastric cancer therapies and as a contender for further in vitro and in vivo investigations.
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发表时间: 2000-11-23
期刊: NATURE
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影响因子: 2.9
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DOI: 10.1083/jcb.152.3.519
发表时间: 2001-02-05
期刊: The Journal of cell biology
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